The overall goal of this project is to develop a commercially viable system for selective gene delivery to growing endothelial cells. Growth of endothelial cells underlies angiogenesis that occurs almost exclusively in pathological situations and is promoted by the endothelial call specific cytokine vascular endothelial growth factor (VEGF). In Phase I we propose to develop a new methodology for VEGF-mediated gene delivery that eliminates direct chemical treatment of the growth factor or DNA, and dramatically increases the load of DNA per VEGF molecule. In Phase II studies we will pursue the following aims: selection of genes that selectively affect growing endothelial cells, testing VEGF fusion proteins for gene delivery in animal models, and developing a commercially viable VEGF fusion protein vehicle for gene therapy. PROPOSED COMMERCIAL APPLICATION: The gene delivery vehicle developed as a result of this project may be used for treatment of several major angiogenesis-dependent pathologies. The methodology developed during this project may be expanded to other cytokine-based therapeutics.